6-72197050-A-G

Position:

• chr6-72197050-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_014989.7(RIMS1):​c.1678+13901A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.526 in 151,908 control chromosomes in the GnomAD database, including 22,770 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.53 (22770 hom., cov: 31)
• Consequence: RIMS1 NM_014989.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.707

Genes affected

RIMS1 (HGNC:17282): (regulating synaptic membrane exocytosis 1) The protein encoded by this gene is a RAS gene superfamily member that regulates synaptic vesicle exocytosis. This gene also plays a role in the regulation of voltage-gated calcium channels during neurotransmitter and insulin release. Mutations have suggested a role cognition and have been identified as the cause of cone-rod dystrophy type 7. Multiple transcript variants encoding different isoforms have been described for this gene. [provided by RefSeq, Mar 2012]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.78).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.804 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RIMS1	NM_014989.7	c.1678+13901A>G		intron_variant		ENST00000521978.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RIMS1	ENST00000521978.6	c.1678+13901A>G		intron_variant		1	NM_014989.7	A2

Frequencies

GnomAD3 genomes AF: 0.526 AC: 79820 AN: 151790 Hom.: 22730 Cov.: 31

Gnomad AFR AF: 0.728

Gnomad AMI AF: 0.544

Gnomad AMR AF: 0.548

Gnomad ASJ AF: 0.426

Gnomad EAS AF: 0.825

Gnomad SAS AF: 0.485

Gnomad FIN AF: 0.383

Gnomad MID AF: 0.506

Gnomad NFE AF: 0.405

Gnomad OTH AF: 0.522

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.526 AC: 79929 AN: 151908 Hom.: 22770 Cov.: 31 AF XY: 0.525 AC XY: 38957 AN XY: 74220

Gnomad4 AFR AF: 0.729

Gnomad4 AMR AF: 0.548

Gnomad4 ASJ AF: 0.426

Gnomad4 EAS AF: 0.825

Gnomad4 SAS AF: 0.485

Gnomad4 FIN AF: 0.383

Gnomad4 NFE AF: 0.405

Gnomad4 OTH AF: 0.525

Alfa AF: 0.448 Hom.: 4450

Bravo AF: 0.551

Asia WGS AF: 0.680 AC: 2365 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
CADD	Benign	5.0
DANN	Benign	0.86

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs2249625; hg19: chr6-72906753;